What is the recommended treatment for Community-Acquired Pneumonia (CAP)?

Community-Acquired Pneumonia Treatment

For outpatients without comorbidities, treat with a macrolide (azithromycin or clarithromycin) as first-line therapy; for those with comorbidities or recent antibiotic use, use a respiratory fluoroquinolone (levofloxacin 750 mg) or a β-lactam plus macrolide combination. 1

Outpatient Treatment Algorithm

Previously Healthy Patients (No Risk Factors for Drug-Resistant S. pneumoniae)

• Macrolide monotherapy (azithromycin, clarithromycin, or erythromycin) is the preferred first-line option 1
• Doxycycline is an acceptable alternative, though with weaker evidence 1
• The British Thoracic Society recommends high-dose amoxicillin as an alternative preferred agent 2, 3

Patients with Comorbidities or Risk Factors

Risk factors include: chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppression; or antimicrobial use within the previous 3 months 1

Choose one of the following regimens:

• Respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin 750 mg) as monotherapy 1
• β-lactam plus macrolide combination: High-dose amoxicillin (1 g three times daily) or amoxicillin-clavulanate (2 g twice daily) PLUS a macrolide 1
• Alternative β-lactams include ceftriaxone, cefpodoxime, or cefuroxime (500 mg twice daily) 1

Critical caveat: In regions with high-level macrolide-resistant S. pneumoniae (≥25% with MIC ≥16 mg/mL), use the combination or fluoroquinolone regimens even for previously healthy patients 1

Inpatient Non-ICU Treatment

For hospitalized patients not requiring ICU admission, use either:

• Respiratory fluoroquinolone monotherapy 1, 3
• β-lactam plus macrolide combination: Preferred β-lactams are cefotaxime, ceftriaxone, or ampicillin; ertapenem for selected patients with risk factors for gram-negative pathogens (excluding Pseudomonas) 1
• Doxycycline may substitute for the macrolide 1
• For penicillin-allergic patients, use a respiratory fluoroquinolone 1

The British Thoracic Society recommends combined oral therapy with amoxicillin plus a macrolide (erythromycin or clarithromycin) for most non-severe inpatients 2, 3

Inpatient ICU Treatment (Severe CAP)

All severe CAP patients require combination therapy with a β-lactam PLUS either azithromycin or a fluoroquinolone 1, 3

Standard Severe CAP Regimen

• β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) PLUS
• Either azithromycin OR a respiratory fluoroquinolone (levofloxacin 750 mg) 1, 4
• For penicillin-allergic patients: respiratory fluoroquinolone plus aztreonam 1

Risk Factors for Pseudomonas aeruginosa

If Pseudomonas infection is suspected, use:

• Antipneumococcal, antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS
• Either ciprofloxacin or levofloxacin (750 mg) 1, 3
• OR the above β-lactam PLUS an aminoglycoside AND azithromycin 1
• OR the above β-lactam PLUS an aminoglycoside AND an antipneumococcal fluoroquinolone 1

Community-Acquired MRSA

• Add vancomycin or linezolid to the regimen if CA-MRSA is suspected 1, 3

Timing and Administration

Time to First Dose

• For patients admitted through the emergency department, administer the first antibiotic dose while still in the ED 1, 3
• For outpatients referred to hospital with life-threatening illness or expected admission delays >2 hours, general practitioners should administer antibiotics immediately 3

Switching from IV to Oral Therapy

Switch to oral therapy when the patient meets ALL of the following criteria:

• Hemodynamically stable and clinically improving 1, 3
• Able to ingest medications 1, 3
• Normally functioning gastrointestinal tract 1, 3
• Inpatient observation while receiving oral therapy is unnecessary; discharge when clinically stable 1

Duration of Therapy

Patients should be treated for a minimum of 5 days 1, 2, 3

Before discontinuing therapy, patients must:

• Be afebrile for 48–72 hours 1, 2, 3
• Have no more than 1 CAP-associated sign of clinical instability 1, 2

A longer duration may be needed if:

• Initial therapy was not active against the identified pathogen 1, 3
• Complicated by extrapulmonary infection (meningitis, endocarditis) 1, 3

Recent evidence from hospitalized patients suggests a minimum of 3 days for β-lactam/macrolide combination therapy in those without resistant bacteria risk factors 4

Pathogen-Directed Therapy

• Once a pathogen is reliably identified through microbiological methods, narrow antimicrobial therapy to target that specific organism 1, 2, 3
• Early treatment within 48 hours of symptom onset is recommended 1, 3

Special Considerations for Severe CAP

Corticosteroids

• Systemic corticosteroid administration within 24 hours of severe CAP development may reduce 28-day mortality 4
• Hypotensive, fluid-resuscitated patients should be screened for occult adrenal insufficiency 1

Respiratory Support

• Patients with hypoxemia or respiratory distress should receive a cautious trial of noninvasive ventilation unless severe hypoxemia (PaO₂/FiO₂ ratio <150) and bilateral infiltrates require immediate intubation 1, 3
• Use low-tidal-volume ventilation (6 mL/kg ideal body weight) for patients with diffuse bilateral pneumonia or ARDS 1, 2, 3

Septic Shock Management

• Patients with persistent septic shock despite adequate fluid resuscitation should be considered for drotrecogin alfa activated within 24 hours of admission 1, 3

Testing and Follow-Up

• All patients should be tested for COVID-19 and influenza when these viruses are circulating in the community, as diagnosis affects treatment and infection prevention strategies 4
• Clinical review should be arranged at approximately 6 weeks with either the general practitioner or in a hospital clinic 2, 3
• Chest radiograph at follow-up is recommended for patients with persistent symptoms, physical signs, or higher risk of underlying malignancy (especially smokers and those >50 years) 3

Common Pitfalls to Avoid

• Do not use macrolide monotherapy for hospitalized patients—combination therapy or fluoroquinolone monotherapy is required 1
• Do not delay antibiotics in the ED—administration should occur before admission 1, 3
• Do not continue IV therapy once oral switch criteria are met—unnecessary prolonged hospitalization increases costs and complications 1
• Do not use azithromycin for IV CAP treatment beyond 1-2 days—switch to oral therapy at 500 mg daily to complete 7-10 days total 5